Open AccessMacrophages attenuate the transcription of CYP1A1 in breast tumor cells and enhance their proliferation
Author(s) -
Sofia Winslow,
Anica Scholz,
Peter Rappl,
Thilo F. Brauß,
Claudia Mertens,
Michaela Jung,
Andreas Weigert,
Bernhard Brüne,
Tobias Schmid
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0209694
Subject(s) - immune system , tumor microenvironment , biology , macrophage , cancer research , tumor progression , innate immune system , tumor infiltrating lymphocytes , mammary tumor , cytotoxic t cell , cell culture , immunology , breast cancer , cancer , immunotherapy , in vitro , biochemistry , genetics
While aberrant cells are routinely recognized and removed by immune cells, tumors eventually escape innate immune responses. Infiltrating immune cells are even corrupted by the tumor to acquire a tumor-supporting phenotype. In line, tumor-associated macrophages are well-characterized to promote tumor progression and high levels of tumor-infiltrating macrophages are a poor prognostic marker in breast cancer. Here, we aimed to further decipher the influence of macrophages on breast tumor cells and determined global gene expression changes in three-dimensional tumor spheroids upon infiltration of macrophages. While various tumor-associated mRNAs were upregulated, expression of the cytochrome P450 family member CYP1A1 was markedly attenuated. Repression of CYP1A1 in tumor cells was elicited by a macrophage-shaped tumor microenvironment rather than by direct tumor cell-macrophage contacts. In line with changes in RNA expression profiles, macrophages enhanced proliferation of the tumor cells. Enhanced proliferation and macrophage presence further correlated with reduced CYP1A1 expression in patient tumors when compared with normal tissue. These findings are of interest in the context of combinatory therapeutic approaches involving cytotoxic and immune-modulatory compounds.